Delta 9-Tetrahydrocannabanol (THC) and other cannabanoids stimulate the production of prostaglandin E2 (PGE2) and prostaglandin F2Alpha in many tissues outside the central nervous system (CNS). There have been essentially no studies on the effects of THC and congeners on prostaglandin (PG) production in the CNS. Since PG formation is regulated by the release from phospholipids of the PG precursor, arachidonic acid (AA), the effects of THC and its congeners on the metabolism of phospholipids, neutral lipids, AA, and PGs will be studied. Brain cortex slices will be prelabelled with [14C]AA (or [3H]AA), followed by its removal by washing with bovine serum albumin. The slices will then be incubated without and with THC and in some cases other cannabanoids, followed by estimation of radioactivity in the above compounds. A balance sheet of [14C]Aa lost and [14C]AA gained in these substances will be set up. In this way, it will be possible to determine whether THC and congeners stimulate release of [14C]AA from lipids and whether pertinent PGs are formed. The THC-stimulated production of PGs in brain cortex slices will also be assayed by radioimmunoassay. The mechanism of release of AA from phospholipids [either release of AA by phospholipase C (PLPase C) followed by diglyceride lipase, or direct deacylation by phospholipase A2 (PLPase A2)] will also be determined. The PLPase C pathway can be shown by a rise in [14C]arachidonoyl-DG, which increases still further in the presence of the specific DG-lipase inhibitor, RHC 80267. Inhibition of the release of free [14C]Aa by RHC 80267 would also be expected. The PLPase A2 pathway can be seen by transient rises in pertinent lysophosphatides (e.g., lysophosphatidyl inositol) after prelabelling with either [32P]orthophosphate, [14C]glycerol, or appropriate phospholipid headgroups (e.g., [3H]myoinositol). The effects of various cannabanoids on phospholipid breakdown and formation of AA and PGs will be compared with their abilities to produce cataleptic effects in rhesus monkeys and "highs" in humans obtained from the literature. Since there is already evidence that PG synthetase (cyclooxygenase) inhibitors, such as aspirin, inhibit some central effects of THC in man and animals (e.g., the cataleptic effect in mice), these studies may have relevance to molecular pharmacological effects of cannabanoids under the usual conditions of marihuana smoking or ingestion.